Cancer stem cells in lung cancer: Evidence and controversies

The cancer stem cell (CSC) model is based on a myriad of experimental and clinical observations suggesting that the malignant phenotype is sustained by a subset of cells characterized by the capacity for self‐renewal, differentiation and innate resistance to chemotherapy and radiation. CSC may be responsible for disease recurrence after definitive therapy and may therefore be functionally synonymous with minimal residual disease. Similar to other solid tumours, several putative surface markers for lung CSC have been identified, including CD133 and CD44. In addition, expression and/or activity of the cytoplasmic enzyme aldehyde dehydrogenase ALDH and capacity of cells to exclude membrane permeable dyes (known as the ‘side population’) correlate with stem‐like function in vitro and in vivo. Embryonic stem cell pathways such as Hedgehog, Notch and WNT may also be active in lung cancers stem cells and therefore may be therapeutically targetable for maintenance therapy in patients achieving a complete response to surgery, radiotherapy or chemotherapy. This paper will review the evidence regarding the existence and function of lung CSC in the context of the experimental and clinical evidence and discuss some ongoing controversies regarding this model.     

Appraisal of anti-arthritic and nephroprotective potential of Cuscuta reflexa

Context: Cuscuta reflexa Roxb. (Cuscutaceae) has been used traditionally for treating sore knees and kidney problems, but its efficacy has not been scientifically examined in treating arthritis and nephrotoxicity.

Objective: Present study determines antiarthritic and nephroprotective potential of the aqueous methanolic extract of Cuscuta reflexa (AMECR).

Materials and methods: Antiarthritic activity of Cuscuta reflexa in formaldehyde and turpentine oil-induced rat arthritis models was appraised at 200, 400 and 600?mg/kg doses for 10 days and 6?h period, respectively, and in vitro protein denaturation (bovine serum albumin, egg albumin) inhibition was studied at 25–800?μg/mL concentration. The nephroprotective effect involved gentamicin-induced nephrotoxicity in rats at 200, 400 and 600?mg/kg doses.

Results: Plant extract at 600?mg/kg significantly reduced paw oedema and joint swelling with maximal inhibition of 71.22% at the 6th hour for turpentine oil and 76.74% on 10th day for formaldehyde. Likewise, in vitro results corroborated significant concentration-dependent increase in percentage protection at 800?μg/mL against both bovine serum albumin (89.30%) and egg albumin (93.51%) denaturation. Similarly, 600?mg/kg dose showed maximum nephroprotection by reducing serum urea (41.400?±?0.510?mg/dL), uric acid (0.740?±?0.032?mg/dL), blood urea nitrogen (18.370?±?0.328), creatinine (3.267?±?0.076) and minimizing kidney weight gain (0.586?±?0.005) and histopathological alterations on 8th day. Furthermore, phytochemical and HPLC analysis revealed the presence of important phytoconstituents.

Discussion and conclusions: These results suggest that AMECR provides protection against arthritis and nephrotoxicity that might be due to the existence of phytoconstituents, thus supporting folkloric claim.     

Novel acetamide derivatives of 2-aminobenzimidazole prevent inflammatory arthritis in rats via suppression of pro-inflammatory mediators

Inflammopharmacology - Benzimidazole ring system is an important pharmacophore with diverse pharmacological activities. In this study, we explored the anti-arthritic effects of newly synthesized...     

Changes in aldehyde dehydrogenase-1 expression during neoadjuvant chemotherapy predict outcome in locally advanced breast cancer

Introduction

Although neoadjuvant chemotherapy (NAC) for locally advanced breast cancer can improve operability and local disease control, there is a lack of reliable biomarkers that predict response to chemotherapy or long-term survival. Since expression of aldehyde dehydrogenase-1 (ALDH1) is associated with the stem-like properties of self-renewal and innate chemoresistance in breast cancer, we asked whether expression in serial tumor samples treated with NAC could identify women more likely to benefit from this therapy.

Methods

Women with locally advanced breast cancer were randomly assigned to receive four cycles of anthracycline-based chemotherapy, followed by four cycles of taxane therapy (Arm A), or the same regimen in reverse order (Arm B). Tumor specimens were collected at baseline, after four cycles, and then at surgical resection. ALDH1 expression was determined by immunohistochemistry and correlated with tumor response using Fisher’s exact test while Kaplan-Meier method was used to calculate survival.

Results

A hundred and nineteen women were enrolled into the study. Fifty seven (48%) were randomized to Arm A and 62 (52%) to Arm B. Most of the women (90%) had ductal carcinoma and 10% had lobular carcinoma. Of these, 26 (22%) achieved a pathological complete response (pCR) after NAC. There was no correlation between baseline ALDH1 expression and tumor grade, stage, hormone receptor, human epidermal growth factor receptor 2 (HER2) status and Ki67 index. ALDH1 negativity at baseline was significantly associated with pCR (P = 0.004). The presence of ALDH1(+) cells in the residual tumor cells in non-responding women was strongly predictive of worse overall survival (P = 0.024). Moreover, serial analysis of specimens from non-responders showed a marked increase in tumor-specific ALDH1 expression (P = 0.028). Overall, there was no survival difference according to the chemotherapy sequence. However, poorly responding tumours from women receiving docetaxel chemotherapy showed an unexpected significant increase in ALDH1 expression.

Conclusions

ALDH1 expression is a useful predictor of chemoresistance. The up-regulation of ALDH1 after NAC predicts poor survival in locally advanced breast cancer. Although the chemotherapy sequence had no effect on overall prognosis, our results suggest that anthracycline-based chemotherapy may be more effective at targeting ALDH1(+) breast cancer cells.

Trial registration

ACTRN12605000588695     

Traditional medicines of plant origin used for the treatment of inflammatory disorders in Pakistan:A review

OBJECTIVE:To pool data on ethnobotanical medicine for the treatment of inflammatory disorders in Pakistan.METHODS:We reviewed 237 research publications based on data from the six provinces in Pakistan(Punjab = 85,Khyber Pakhtunkhwa = 65,Sindh =15,Balochistan = 8,Gilgit Baltistan = 22,Azad Jammu and Kashmir = 42) published until June 2015 in various journals.This was achieved using seven online databases:Science Direct,Google,Google Scholar,Pub Med,Wiley Online Library,SpringerLink,and MEDLINE.Data were analyzed from different perspectives.RESULTS:People from Pakistan made use of 371 plant species belonging to 263 genera and 99 families for the treatment of inflammatory disorders.Plants from the Asteraceae family were used most often.Herbs were the dominant growth form.Leaves were the plant parts used most often.Decoctions were the main preparation method.Nine plant species were used most frequently in thedwellers of most regions of Pakistan.A total of 111 plants were shown experimentally to have neither anti-arthritic nor anti-inflammatory activities,and148 plant species were threatened.Eighty-four species had commercial importance.Twelve plant species were imported,and 25 plant species were exported,from Pakistan.CONCLUSION:This review provides baseline data for plant species in Pakistan that have potential anti-inflammatory/anti-arthritic activities.     

Indigenous medicinal plants of Pakistan used to treat skin diseases: a review

Ethno-pharmacological relevance

Plants are providing reliable therapy since time immemorial. Pakistan has a great diversity in medicinal flora and people use these ethno-medicines to deal with many skin problems. This review explores the fundamental knowledge on various dermatological properties of medicinal plants of Pakistan and is aimed to provide a baseline for the discovery of new plants having activities against skin issues.

Material and method

A total of 244 published articles were studied using different research engines like PubMed, Google, Google-scholar and science direct.

Results

Review of literature revealed ethno-pharmacological use of 545 plant species, belonging to 118 families and 355 genera, to combat various skin ailments. Out of these, ten most commonly used plant species belonging to ten different families are documented in this review. It was also found out that ehno-medicines are prepared using various parts of the plants including leaves (28.32%), whole plant and roots 13.17% and 10.97% respectively, in the form of powder (23.5%) and paste (22.75%). A total of 13 endangered plant species and ten commercially important plants were recorded.

Conclusion

Medicinal plants of Pakistan have therapeutic effects against several skin problems; however most of medicinal plants are still not evaluated scientifically to support their ethno-pharmacological claim on skin. Dermatological pathogens are recommended to study. Further, the conservational programs should be established for endangered species.

     

Pharmacological evaluation of anti-arthritic potential of terpinen-4-ol using in vitro and in vivo assays

Inflammopharmacology - Terpinen 4-ol, a phytochemical is a monoterpene which has been reported for its anti-inflammatory effect. Present research was planned to check its effect against arthritis...     

Anti-rheumatic activity of pseudoephedrine (a substituted phenethylamine) in complete Freund’s adjuvant-induced arthritic rats by down regulating IL-1β, IL-6 and TNF-α as well as upregulating IL-4 and IL-10

Inflammopharmacology - Pseudoephedrine (substituted phenethylamine) is well known as psychotic and bronchodilator. Numerous studies on phenethylamine derivatives indicated that these agents have...     

Evaluation of antihypertensive potential of Ficus carica fruit

Context: Ficus carica L. (Moraceae) fruit is said to possess cardiovascular activity and has been used empirically in traditional phytotherapies for the treatment of hypertension and various other cardiovascular diseases.

Objective: This study investigated the antihypertensive and cardioinhibitory activity of the aqueous-methanol extract of F. carica fruit in rats.

Materials and methods: Extract in 250, 500 and 1000?mg/kg doses (p.o.) were administered to normotensive Sprague Dawley rats and blood pressure was measured using non-invasive technique. Hypertension was induced in rats by oral administration of 10% glucose for 3 weeks. Hypotensive effect of extract (1000?mg/kg p.o) was studied in normotensive and glucose-treated hypertensive rats. Langendorff’s isolated heart technique was used to assess the effect of crude extract on force of contraction and heart rate. In addition, antioxidant potential, TPC, TFC were also assessed by DPPH free radical scavenging activity, Folin–Ciocalteu reagent and AlCl₃ assay, respectively. Furthermore, phenolic compounds were analyzed using HPLC-DAD technique.

Results and discussion: The 1000?mg/kg dose decreased blood pressure significantly in normotensive and glucose-treated hypertensive rats. The isolated heart study showed that the extract produced negative inotropic and chronotropic effects but it failed to block the stimulatory effect of both adrenaline and CaCl₂. HPLC studies on the F. carica extract indicated the presence of quercetin, gallic acid, caffeic acid, vanillic acid, syringic acid, coumaric acid and chromotropic acid.

Conclusions: This study demonstrated that aqueous methanol extract of F. carica fruit exerted hypotensive and antihypertensive effects in glucose-induced hypertensive rats.     

Traditional medicinal plants used for respiratory disorders in Pakistan: a review of the ethno-medicinal and pharmacological evidence

Respiratory disorders are a common cause of malady and demise in Pakistan due to its remoteness, cold and harsh climatic conditions as well as scarce health care facilities. The people rely upon the indigenous plant resources to cure various respiratory disorders. The primary objective of this review was to assemble all available ethno-medicinal data of plants used for respiratory disorders in Pakistan. Pharmacological activity of these plants (based upon published scientific research), distribution, diversity, use, preparation methods, economical value, conservation status and various available herbal products of some plants have also been explored. This study scrutinized various electronic databases for the literature on medicinal plants used in Pakistan to treat respiratory disorders. A total of 384 species belonging to 85 families used to treat respiratory disorders in Pakistan has been documented. Cough was the disorder treated by the highest number of species (214) followed by asthma (150), cold (57) and bronchitis (56). Most of the plants belongs to Asteraceae (32) and Solanaceae family (32) followed by moraceae (17), Poaceae (13), and Amaranthaceae (13) with their habit mostly of herb (219) followed by Shrub (112) and tree (69). Traditional healers in the region mostly prepare ethno medicinal recipes from leaves (24%) and roots (11%) in the form of decoction. Among the reported conservation status of 51 plant species, 5 were endangered, 1 critically endangered, 11 vulnerable, 14 rare, 16 least concern, 3 infrequent and 1 near threatened. We found only 53 plants on which pharmacological studies were conducted and 17 plants being used in herbal products available commercially for respiratory disorders. We showed the diversity and importance of medicinal plants used to treat respiratory disorders in the traditional health care system of Pakistan. As such disorders are still causing several deaths each year, it is of the utmost importance to conduct phytochemical and pharmacological studies on the most promising species. It is also crucial to increase access to traditional medicine, especially in rural areas. Threatened species need special attention for traditional herbal medicine to be exploited sustainably.